Developmental exposure to methyl ester sulfonate induces autism-like behavioral deficits in mice by dysregulation of the Notch/Hes signaling pathway disrupting neuronal differentiation.

Scientists exposed pregnant mice to a common chemical surfactant (MES) found in the environment. The baby mice showed autism-like behaviors including social difficulties, anxiety, and repetitive behaviors. The chemical appeared to disrupt brain development by interfering with how brain cells grow and connect to each other. This suggests environmental chemicals might contribute to autism development, though this was only tested in mice.

This animal study investigated developmental exposure to methyl ester sulfonate (MES), an environmental surfactant, and its potential contribution to autism-like behaviors. Pregnant mice exposed to environmentally relevant MES doses showed offspring with dose-dependent autism-like behavioral deficits including impaired social interactions, increased anxiety, and repetitive behaviors. The study identified disruption of the Notch/Hes signaling pathway as a key mechanism, leading to impaired neuronal differentiation and synaptogenesis. Neuropathological changes included blood-brain barrier disruption, neuronal loss, and reduced dendritic spine density.

Molecular analysis suggested direct MES interaction with Notch receptors, and in vitro studies confirmed suppressed neural stem cell differentiation.

Highlights potential role of environmental surfactants in autism development through disrupted brain cell development. Suggests need for toxicological assessment of common environmental chemicals and consideration of prenatal environmental exposures in autism research and prevention strategies.

Animal model findings may not directly translate to humans. Sample size not reported. Single environmental toxicant studied - real-world exposure involves multiple chemicals. Behavioral assessments limited to mouse models of autism-like behaviors rather than comprehensive autism phenotypes.

Developmental exposure to environmental pollutants is increasingly recognized as a significant risk factor for autism spectrum disorder (ASD), yet the specific mechanisms by which individual toxicants contribute to this neurodevelopmental disorder remain largely unknown. Methyl ester sulfonate (MES), a widely used anionic surfactant with widespread environmental detection, lacks comprehensive evaluation for developmental neurotoxicity. Here, we exposed pregnant mice to environmentally relevant MES doses (0.06-6 mg/L) from gestational day 8.5 (GD8.5) to postnatal day 21.5 (PND21.5) and assessed their offspring for neurodevelopmental changes. Results showed dose-dependent ASD-like behavioral deficits, including impaired social interactions, heightened anxiety-like behaviors, and increased repetitive/stereotypic patterns.

These behavioral anomalies were accompanied by neuropathological alterations, including blood-brain barrier disruption, neuronal loss, and reduced dendritic spine density, indicative of impaired synaptogenesis. Integrative transcriptomic analysis of hippocampal tissue revealed significant dysregulation of key pathways involved in neurodevelopment, prominently featuring the Notch/Hes signaling pathway. Molecular docking simulations suggested that MES could directly interact with Notch receptors, potentially disrupting ligand-receptor interactions. Further in vitro experimental validation demonstrated that MES exposure suppressed neural stem cell differentiation.

Collectively, these findings provided evidence that early-life MES exposure acts as a neurodevelopmental toxicant by disrupting Notch/Hes signaling, thereby impairing neuronal differentiation and synaptogenesis, which underlined the observed ASD-like behavioral deficits in mice. This study offers novel mechanistic insights into how environmental factors contribute to ASD pathogenesis and highlights the need for toxicological assessment of widely distributed surfactants.